In summary, our results indicate that interferon induction by poly(I.C) in human fibroblasts is a multi-step process, where the initial interaction of the inducer with the sensitive cell is not rate limiting. Poly(I.C) induces, in this system, the synthesis of specific interferon mRNA which can be translated with fidelity in heterologous cell systems and cell-free systems. It was shown that human interferon is coded for by a poly(A)-containing mRNA sedimenting between 7-10S. This RNA also stimulated (H3)amino acid incorporation in cell-free protein synthesis systems prepared from the Krebs-II ascites tumor, and the proteins produced in the cell-free system were able to inhibit the VSV replication in human fibroblast cells. The results further indicate that the antiviral effect of poly(I.C) is interferon mediated and that interferon produces the antiviral state by interaction with the external part of the cellular membrane.